ArticleOncogene2012
Sox2 maintains self renewal of tumor-initiating cells in osteosarcomas.
Article in Oncogene, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 144 papers.
What it found
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
144 citing papers in PubMed, 242 citations in OpenAlex.
- Sox2 expression predicts poor survival of hepatocellular carcinoma patients and it promotes liver cancer cell invasion by activating Slug.Medical oncology (Northwood, London, England) · 2013Trial
- miR-424-5p Regulates Stem-like and Malignant Phenotypes in Osteosarcoma by Targeting FZD4.Cancers · 2026Article
- Regulatory roles of non-coding and exosomal RNAs in colorectal cancer: spotlight on angiogenesis.Clinical and experimental medicine · 2025Review
- Signaling pathways as the pivotal regulators of cisplatin resistance in tumor cells through SOX2 upregulation.Medical oncology (Northwood, London, England) · 2025Review
- The Role of Deubiquitinating Enzymes in Primary Bone Cancer.Molecular biotechnology · 2025Review
- Cancer stem cells and niches: challenges in immunotherapy resistance.Molecular cancer · 2025Review
- Targeting AKT as a promising strategy for SOX2-positive, chemoresistant osteosarcoma.Bone research · 2025Article
- Thrombospondin 1 Promotes Cytoskeleton Remodeling, Dedifferentiation, and Pulmonary Metastasis through ITGA1 and ITGA6 in Osteosarcoma.International journal of biological sciences · 2025Article
- Dysregulation of the p53 pathway provides a therapeutic target in aggressive pediatric sarcomas with stem-like traits.Cellular oncology (Dordrecht, Netherlands) · 2024Article
- FOSL1 promotes stem cell‑like characteristics and anoikis resistance to facilitate tumorigenesis and metastasis in osteosarcoma by targeting SOX2.International journal of molecular medicine · 2024Article
- SOX2 and OCT4 mediate radiation and drug resistance in pancreatic tumor organoids.Cell death discovery · 2024Article
- Nε-(1-Carboxymethyl)-L-lysine/RAGE Signaling Drives Metastasis and Cancer Stemness through ERK/NFκB axis in Osteosarcoma.International journal of biological sciences · 2024Article
- Targeting the SOX2/CDP protein complex with a peptide suppresses the malignant progression of esophageal squamous cell carcinoma.Cell death discovery · 2023Article
- Clinical perspectives and outcomes of the giant breast phyllodes tumor and sarcoma: a real-world retrospective study.BMC cancer · 2023Article
- Cellular and Genetic Background of Osteosarcoma.Current issues in molecular biology · 2023Review
- Cancer Stem Cells in Sarcomas: In Vitro Isolation and Role as Prognostic Markers: A Systematic Review.Cancers · 2023Review
- KPT6566 induces apoptotic cell death and suppresses the tumorigenicity of testicular germ cell tumors.Frontiers in cell and developmental biology · 2023Article
- Low Doses of Bisphenol A Disrupt Neuronal Differentiation of Human Neuronal Stem/Progenitor Cells.Acta histochemica et cytochemica · 2022Article
- Identification of a neural development gene expression signature in colon cancer stem cells reveals a role foriScience · 2022Article
- SETD1A-SOX2 axis is involved in tamoxifen resistance in estrogen receptor α-positive breast cancer cells.Theranostics · 2022Article
84 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
Abstract
Tumors are thought to be sustained by a reservoir of self-renewing cells, termed tumor-initiating cells or cancer stem cells. Osteosarcomas are high-grade sarcomas derived from osteoblast progenitor cells and are the most common pediatric bone malignancy. In this report we show that the stem cell transcription factor Sox2 is highly expressed in human and murine osteosarcoma (mOS) cell lines as well as in the tumor samples. Osteosarcoma cells have increased ability to grow in suspension as osteospheres, that are greatly enriched in expression of Sox2 and the stem cell marker, Sca-1. Depletion of Sox2 by short-hairpin RNAs in independent mOS-derived cells drastically reduces their transformed properties in vitro and their ability to form tumors. Sox2-depleted osteosarcoma cells can no longer form osteospheres and differentiate into mature osteoblasts. Concomitantly, they exhibit decreased Sca-1 expression and upregulation of the Wnt signaling pathway. Thus, despite other mutations, these cells maintain a requirement for Sox2 for tumorigenicity. Our data indicate that Sox2 is required for osteosarcoma cell self renewal, and that Sox2 antagonizes the pro-differentiation Wnt pathway that can in turn reduce Sox2 expression. These studies define Sox2 as a survival factor and a novel biomarker of self renewal in osteosarcomas, and support a tumor suppressive role for the Wnt pathway in tumors of mesenchymal origin. Our findings could provide the basis for novel therapeutic strategies based on inhibiting Sox2 or enhancing Wnt signaling for the treatment of osteosarcomas.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.